Steroids and stones may break my bones

High daily doses of inhaled costicosteroids found to increase risk of fractures in COPD patients

By William Donaldson

Despite more public awareness on the dangers of smoking, chronic obstructive pulmonary disease (COPD) continues to be among the most common diseases seen by family physicians. Major developments in treatments over the past few years have helped arm physicians with an arsenal of options to fight COPD. A new study, however, spells bad news for patients on high-dose inhaled corticosteroids (ICS) � one option shown to improve symptoms. People on ICS run an elevated risk of nonvertebral fractures, according to a large US study of veterans. The findings of this trial are published in the April issue of the American Journal of Respiratory and Critical Care Medicine.

The researchers say their findings are hardly unexpected, since ICS has been shown to have a negative effect on biochemical markers of bone creation and resorption. Also, COPD patients are already at elevated risk of osteoporosis from smoking, sedentary lifestyles, and systemic corticosteroids.

The investigators identified 1,708 cases of nonvertebral fractures among 40,157 Veterans Affairs patients diagnosed with COPD. These fracture victims were matched to 6,817 controls for comparison. The average age of patients in the study was 62.7 years, and 94% were male.

Use of ICS was assessed from prescription records, and doses were converted to beclamethasone equivalents. When the study parameter was exposure to ICS at any time during the research, there was no association whatsoever with increased fracture risk. But when patients, who were current high-dose ICS users, were considered alone, the risk of nonvertebral fracture was found to be 68% higher than in unexposed patients. A high dose was taken as anything over 700µg daily.

Three previous studies have sought to measure fracture risk from ICS. One found ICS use was associated with an elevated risk of nonvertebral fractures with an odds ratio of 1.28 for doses over 700µg beclamethasone equivalent per day. A 2002 study of asthma and COPD patients found that hip fractures were more likely in this group, and the odds ratio was elevated to 1.19 for those taking ICS.

A 2001 study in the New England Journal of Medicine found that ICS were associated with reduced bone mineral density after as little as one year of use. It may be that chronic exposure increases bone resorption. Moreover, short-term exposure may trigger cell death in osteocytes, leaving tiny dead spaces in bone.

The authors conclude, "...the increase in the risk of fracture associated with ICS use found in this study doesn't by itself warrant the stopping of treatment in patients with COPD. However, evidence from this and other epidemiologic studies of ICS dose and the risk of fractures indicate that providers should consider prescribing the lowest effective dose of ICS in the management of COPD."